Adjuvant mFOLFOXIRI after curative-intent resection of oligometastatic colorectal cancer: phase II FANTASTIC trial
Abstract
Background: Patients with oligometastatic colorectal cancer (mCRC) remain at high risk of recurrence after curative surgery, yet the benefit of adjuvant chemotherapy remains inconclusive. This study evaluated the feasibility and efficacy of adjuvant modified (m)FOLFOXIRI (irinotecan, oxaliplatin, L-leucovorin (L-LV), 5-fluorouracil (5-FU)), as well as the utility of circulating tumour DNA (ctDNA) as a prognostic and predictive biomarker in mCRC.
Methods: Between October 2020 and January 2024, patients with histologically confirmed mCRC undergoing complete metastasectomy were enrolled in this multicentre non-randomized phase II study. Eligible and consenting patients received eight cycles of mFOLFOXIRI followed by four cycles of 5-FU/L-LV; ineligible/non-consenting patients received standard of care (SOC; CAPOX (capecitabine and oxaliplatin), 5-FU, or observation). ctDNA was assessed using the tumour-informed personalized Signatera™ assay (Natera, Austin, TX, USA) at 28 days and 7 months after surgery. The primary endpoint was completion of eight cycles of mFOLFOXIRI in a target sample of 36 patients.
Results: Of the 83 registered patients, 73 were enrolled (39 mFOLFOXIRI, 34 SOC). The mFOLFOXIRI completion rate was 74% (80% confidence interval 63% to 83%; P < 0.001). ctDNA positivity predicted significantly inferior recurrence-free survival across both the mFOLFOXIRI and SOC treatment groups at 28 days (hazard ratios (HR) 7.27 and 7.17, respectively) and 7 months (HR 3.96 and 4.38, respectively) after surgery. Multivariate analysis identified ctDNA positivity, RAS mutation, metachronous metastases, and mFOLFOXIRI as significant prognostic factors. mFOLFOXIRI improved recurrence-free survival compared with SOC in the overall population (HR 0.44; P = 0.012), with a trend towards benefit in ctDNA-positive but not ctDNA-negative patients. ctDNA clearance rates were 33% (mFOLFOXIRI) and 20% (SOC).
Conclusions: This study indicates the feasibility of adjuvant mFOLFOXIRI in patients with mCRC, with an acceptable safety profile and potential clinical benefit among those with ctDNA positivity 28 days after surgery.
Related
- Comparative efficacy of common adjuvant treatments after resection of colorectal liver metastases : A systematic review and network meta-analysis
- Surgical resection versus stereotactic body radiotherapy for oligometastatic breast cancer to the liver.
- Factors Associated with Adjuvant Radiotherapy Use After Simpson Grade I Resection of WHO Grade 2 Meningioma: A Single-Center Retrospective Cohort Study
- Prognostic Significance of the ESTRO/EORTC Classification of Oligometastatic Disease for Colorectal Cancer Patients With Uncommon Metastases Treated With Definitive Radiotherapy
- Treatment of oligometastatic disease in colorectal cancer: from molecular biology to multimodal strategies.
BibTeX
@article{kataoka2026adjuvant,
title = {{Adjuvant mFOLFOXIRI after curative-intent resection of oligometastatic colorectal cancer: phase II FANTASTIC trial}},
author = {Kozo Kataoka and Takeshi Yamada and Kentaro Yamazaki and Shintaro Kanaka and Takeshi Suto and Manabu Shiozawa and Yasumasa Takii and Masayoshi Yasui and Toshifumi Yamaguchi and Nobuhisa Matsuhashi and Naoto Takase and Kazuma Ito and Erik Spickard and Arkarachai Fungtammasan and Rama S Madhurapantula and Adham Jurdi and Eiji Oki and Hideaki Bando and Yoshiaki Nakamura and Takayuki Yoshino and Masataka Ikeda and Keita Mori and Yukihide Kanemitsu},
journal = {BJS Open},
year = {2026},
month = nov,
doi = {10.1093/bjsopen/zrag144},
url = {https://doi.org/10.1093/bjsopen/zrag144},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Adjuvant mFOLFOXIRI after curative-intent resection of oligometastatic colorectal cancer: phase II FANTASTIC trial
AU - Kozo Kataoka
AU - Takeshi Yamada
AU - Kentaro Yamazaki
AU - Shintaro Kanaka
AU - Takeshi Suto
AU - Manabu Shiozawa
AU - Yasumasa Takii
AU - Masayoshi Yasui
AU - Toshifumi Yamaguchi
AU - Nobuhisa Matsuhashi
AU - Naoto Takase
AU - Kazuma Ito
AU - Erik Spickard
AU - Arkarachai Fungtammasan
AU - Rama S Madhurapantula
AU - Adham Jurdi
AU - Eiji Oki
AU - Hideaki Bando
AU - Yoshiaki Nakamura
AU - Takayuki Yoshino
AU - Masataka Ikeda
AU - Keita Mori
AU - Yukihide Kanemitsu
PY - 2026
DA - 2026/11/04
JO - BJS Open
DO - 10.1093/bjsopen/zrag144
UR - https://doi.org/10.1093/bjsopen/zrag144
AB - Background: Patients with oligometastatic colorectal cancer (mCRC) remain at high risk of recurrence after curative surgery, yet the benefit of adjuvant chemotherapy remains inconclusive. This study evaluated the feasibility and efficacy of adjuvant modified (m)FOLFOXIRI (irinotecan, oxaliplatin, L-leucovorin (L-LV), 5-fluorouracil (5-FU)), as well as the utility of circulating tumour DNA (ctDNA) as a prognostic and predictive biomarker in mCRC. Methods: Between October 2020 and January 2024, patients with histologically confirmed mCRC undergoing complete metastasectomy were enrolled in this multicentre non-randomized phase II study. Eligible and consenting patients received eight cycles of mFOLFOXIRI followed by four cycles of 5-FU/L-LV; ineligible/non-consenting patients received standard of care (SOC; CAPOX (capecitabine and oxaliplatin), 5-FU, or observation). ctDNA was assessed using the tumour-informed personalized Signatera™ assay (Natera, Austin, TX, USA) at 28 days and 7 months after surgery. The primary endpoint was completion of eight cycles of mFOLFOXIRI in a target sample of 36 patients. Results: Of the 83 registered patients, 73 were enrolled (39 mFOLFOXIRI, 34 SOC). The mFOLFOXIRI completion rate was 74% (80% confidence interval 63% to 83%; P < 0.001). ctDNA positivity predicted significantly inferior recurrence-free survival across both the mFOLFOXIRI and SOC treatment groups at 28 days (hazard ratios (HR) 7.27 and 7.17, respectively) and 7 months (HR 3.96 and 4.38, respectively) after surgery. Multivariate analysis identified ctDNA positivity, RAS mutation, metachronous metastases, and mFOLFOXIRI as significant prognostic factors. mFOLFOXIRI improved recurrence-free survival compared with SOC in the overall population (HR 0.44; P = 0.012), with a trend towards benefit in ctDNA-positive but not ctDNA-negative patients. ctDNA clearance rates were 33% (mFOLFOXIRI) and 20% (SOC). Conclusions: This study indicates the feasibility of adjuvant mFOLFOXIRI in patients with mCRC, with an acceptable safety profile and potential clinical benefit among those with ctDNA positivity 28 days after surgery.
SN - 2474-9842
ER -